Water soluble near infrared sensing polymers with low band gaps

ABSTRACT

The present invention is directed to polymeric materials including a copolymer of at least a first and second monomer that have desirable electrical and optical properties, such as a low band gap and near infrared (NIR) absorption, respectively. More specifically, the present invention is directed to polymeric materials with charge neutrality that display increased solubility in aqueous media while retaining their electrical and optical properties. The polymeric materials in accordance with the present invention can be modified with any desired functional group to tailor the polymer materials for a specific application. Also described are methods of making the polymeric materials in accordance with the present invention.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Stage of PCT/US2011/000557, filed Mar.28, 2011, and designating the United States (published in English onSep. 29, 2011, as WO 2011/119239 A1; the title and abstract were alsopublished in English), which claims priority to U.S. Provisional PatentApplication No. 61/318,114, filed Mar. 26, 2010, each hereby expresslyincorporated by reference in its entirety and each assigned to theassignee hereof.

FIELD

The present disclosure relates to polymeric compositions, and relatedmethods and uses.

BACKGROUND

In this specification where a document, act or item of knowledge isreferred to or discussed, this reference or discussion is not anadmission that the document, act or item of knowledge or any combinationthereof was at the priority date, publicly available, known to thepublic, part of common general knowledge, or otherwise constitutes priorart under the applicable statutory provisions; or is known to berelevant to an attempt to solve any problem with which thisspecification is concerned.

Near-infrared (NIR) fluorescent dyes have received attention in recentyears. However, despite the advantages of polymers and their use in theNIR range, the currently available NIR dyes are all small molecules witha single reactive site. NIR polymers, especially water-soluble NIRpolymers with multiple reactive sites and low band gaps are stilllacking. Water solubility is a beneficial property for dyes to be usedin many applications. The use of NIR polymers for such applications hasbeen hampered by lack of water solubility.

A conventional method of making molecules water-soluble is to introducecharges to their molecular structures. Introduction of chargessignificantly enhances water solubility of molecules, like all thecommercially available water-soluble dyes which are charged molecules.However, the presence of charges in molecules could cause potentialinterfering responses due to non-specific electrostatic interactions incomplicated biological samples.

Thus, there is a need in the art for NIR polymers with low band gapsthat demonstrate overall charge neutrality, water solubility andfunctionality.

While certain aspects of conventional technologies have been discussedto facilitate disclosure of the invention, Applicants in no way disclaimthese technical aspects, and it is contemplated that the claimedinvention may encompass or include one or more of the conventionaltechnical aspects discussed herein.

SUMMARY

According to certain aspects of the invention, NIR polymers that combinea low band gap, charge neutrality, water solubility, and functionalityin one package have been developed. These polymers have very good watersolubility while retaining their NIR optical properties and neutrality,which renders them suitable for use in many applications that requirehigh hydrophilic properties or water solubility.

According to certain aspects, the invention provides new materials thatcombines advantages of NIR dyes and multivalent binding functions of apolymer, as well as high water solubility into one package and thusoffers a general and powerful platform suitable for use in numerousapplications. Materials of the present invention may also feature lowband gaps of between about 0.8 eV and about 1.7 eV and NIR opticalproperties.

According to one aspect, the present invention provides new materials ofthe general formulas shown below:

wherein:

M₁=substituted or un-substituted conjugated monomer, short conjugationblock oligomer, alkene, or alkyne;

M₂=substituted or un-substituted monomer, short conjugation blockoligomer, alkene, or alkyne with or without side chains;

=oligo- or poly-ethylene glycol, alkyl chain with or without branches,conjugated chain with or without substitutes;

=single bond, double bond or triple bond;

n=any integer greater than 1; and

R₁ and R₂=any functional group, such as, without limitation, H, CH₃,alkene, alkyne, OH, Br, Cl, I, F, SH, COOH, NH₂, CHO, maleimide, NHSester, any heterocyclic compounds that can form a metal complex, otherapplicable functional groups, and biological molecules such as, withoutlimitation, carbohydrates, proteins, peptides, DNA, RNA, antibodies,antigens, enzymes, bacterias, redox molecules, host molecules, guestmolecules, haptens, lipids, microbes, aptamers, sugars or the like;wherein:

Monomer M₁ and M₂ can have, without limitation, zero, one or more thanone side chain

;

Side chain

in monomer M₁ and M₂, without limitation, can be the same or different,or one side chain has at least one reactive group and another side chainhas no reactive group;

R₁ and R₂, without limitation, can be the same or different, or one isfunctional group and another is non-functional group.

According to one aspect, the present invention provides a polymericmaterial comprising: a copolymer of

a first monomer (1), (2) or (3); and

a second monomer (4), (5), (6) or (7);

wherein,

wherein

-   -   R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (R₂ can be same or        different), SR₂, SR₂COOH, SR₂NH₂, SR₂SO₃H, SR₂SH, SR₂OH,        malemide, or NHS ester,    -   X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, or        substituted heteroaryl, and    -   R₂=Alkyl, aryl or heteroaryl, substituted aryl or substituted        heteroaryl; and

-   -   wherein R₃ and R₄=H or

According to a further aspect, the present invention provides a polymercomprising the polymeric material described immediately above, andfurther comprising a third monomer (11), (12), (13), (14), (15), (16),(17), (18), or (19);

wherein:

wherein R₃ and R₄=H or

According to another aspect, the present invention provides polymericmaterial comprising: a copolymer of

-   -   a first monomer (8), (9) or (10); and    -   a second monomer (4), (5), (6) or (7);

wherein,

wherein

-   -   R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (3R₂ can be same or        different), SR₂, SR₂COOH, SR₂NH₂, SR₂SO₃H, SR₂SH, SR₂OH,        malemide, or NHS ester,    -   X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, or        substituted heteroaryl, and    -   R₂=Alkyl, aryl, heteroaryl, substituted aryl or substituted        heteroaryl;    -   and

wherein R₃ and R₄=H or

According to yet another aspect, the present invention provides apolymeric material comprising: a copolymer of

a first monomer (8), (9) or (10); and

a second monomer (11), (12), (13), (14), (15), (16), (17), (18), or(19);

wherein,

wherein

-   -   R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (3R₂ can be same or        different), SR₂, SR₂COOH, SR₂NH₂, SR₂SO₃H, SR₂SH, SR₂OH,        malemide, or NHS ester,    -   X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, or        substituted heteroaryl, and    -   R₂=Alkyl, aryl, heteroaryl substituted aryl or substituted        heteroaryl;    -   and

wherein R₃ and R₄=H or

The present invention may address one or more of the problems anddeficiencies of the prior art discussed above. However, it iscontemplated that the invention may prove useful in addressing otherproblems and deficiencies, or provide benefits and advantages, in anumber of technical areas. Therefore the claimed invention should notnecessarily be construed as being limited to addressing any of theparticular problems or deficiencies discussed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other feature of this invention will now be described withreference to the drawings of certain embodiments which are intended toillustrate and not to limit the invention.

FIG. 1 shows the level of energy absorption at various wavelengths of apolymeric material formed according to the principles of the presentinvention.

FIG. 2 illustrates the solubility of a polymeric material formedaccording to the principles of the present invention.

FIG. 3 illustrates the solubility of another polymeric material formedaccording to the principles of the present invention.

FIG. 4 shows the level of energy absorption at various wavelengths of apolymeric material formed according to the principles of the presentinvention.

FIG. 5 shows the results of incubation of a polymeric material formedaccording to the principles of the present invention with magneticbeads.

FIG. 6 shows the results of incubation of a comparative material withmagnetic beads.

FIG. 7 shows the combined results of incubation of a material formedaccording to the principles of the present invention and incubation of acomparative polymeric material with magnetic beads.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Further aspects, features and advantages of this invention will becomeapparent from the detailed description which follows.

Polymers or polymer precursors of the present invention can be composedor synthesized according to a number of alternatives. For example,polymers can be formed by co-polymerizing one of the monomers from Table1 and one of the monomers from Table 2. Also, polymers can be formed byco-polymerizing one of the monomers from Table 1, one of the monomersfrom Table 2, and one of the monomers from Table 4. Polymer precursorscan also be synthesized by co-polymerizing one of the monomers fromTable 3, and one of the monomers from Table 2 and/or one of the monomersfrom Table 4. Alternatively, polymer precursors can be synthesized byself-polymerizing a monomer from Table 1, Table 2, Table 3 or Table 4.

TABLE 1

R₁ = OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃, SR₂, SR₂ COOH, SR₂NH2,SR₂SO₃H, X: C₀-C₃ alky, aryl, substitute aryl, SR₂SH, SR₂OH, maleimide,NHS Ester heteroaryl, substituted heteroaryl R₂ = alkyl, aryl,heteroaryl, substituted aryl, substituted heteroaryl

TABLE 2

TABLE 3

R₁ = OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃, SR₂, SR₂ COOH, SR₂NH2,SR₂SO₃H, X: C₀-C₃ alkyl, aryl, substituted aryl, SR₂SH, SR₂OH,maleimide, NHS Ester heteroaryl, substituted heteroaryl R₂ = alky, aryl,heteroaryl, substituted aryl, substituted heteroaryl

TABLE 4

The polymer precursors described above can be functionalized byattaching any suitable functional units such as bio-molecules to itsreactive sites. The polymer is ether soluble in water in its precursorstate or after functionalization. Examples of suitable bio-molecules forfunctionalization may include, without limitation, carbohydrates,proteins, peptides, DNA, RNA, antibodies, antigens, enzymes, bacterias,redox molecules, host molecules, guest molecules, haptens, lipids,microbes, aptamers, sugars or the like. Some specific examples ofpolymer precursors and functionalized polymers with suitablebio-molecules are shown in Table 5.

TABLE 5

R₁ = OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃, SR₂, SR₂ COOH, SR₂NH2,SR₂SO₃H, SR₂SH, SR₂OH, maleimide, NHS Ester R₂ = alkyl, aryl,heteroaryl, substituted aryl, substituted heteroaryl

The wavelength of energy absorbed by the polymers is about 700-1100 nmor above about 1100 nm, and the absorption can be adjusted by adjustingthe degree of polymerization. The band gaps of the polymers aregenerally between about 0.8 eV and about 1.7 eV. In a number of cases,the band gaps are between about 1.1 eV and about 1.4 eV.

The concepts of the present invention will now be further described byreference to the following non-limiting examples of specific polymersand exemplary techniques for their formation. It should be understoodthat additional polymers and additional techniques of formation are alsocomprehended by the present invention.

Example 1 Synthesis of Polymer 1

Scheme 1 below illustrates the synthesis of4,7-dibromo-5,6-diamine-benzo[1,2,5]thiadiazole 4 starting frombenzo[1,2,5]thiadiazole.

Benzothiadiazole (10.0 g, 73.4 mmol) and HBr (150 mL, 48%) were added toa 500 mL three-necked round-bottomed flask. A solution containing Br₂(35.2 g, 220.3 mmol) in HBr (100 mL) was added dropwise very slowly.After the total addition of Br₂, the solution was heated at reflux forovernight. Precipitation of a dark orange solid was noted. The mixturewas cooled to room temperature, and a sufficient amount of a saturatedsolution of NaHSO₃ was added to completely consume any excess Br₂. Themixture was filtered under vacuum and washed exhaustively with water anddried under vacuum to yield the dibrominated product 2, as confirmed bythe following nuclear magnetic resonance (NMR) data obtained therefrom:¹H NMR (500 MHz, CDCl3): δ 7.75 (s, 2H) ppm

4,7-dibromobenzo[1,2,5]thiadiazole 2 (409, 137 mmol) was added to amixture of fuming sulphuric acid (200 ml) and fuming nitric acid (200ml) in small portions at 0° C. and then the reaction mixture was stirredat room temperature for 72 hrs. After 72 hrs, the mixture was pouredinto ice-water, the solid was filtered and washed with water severaltimes, then recrystallized in ethanol to give compound 3 as a paleyellow solid.

A mixture of 4,7-dibromo-5,6-dinitro-benzo[1,2,5]thiadiazole 3 (10 g, 26mmol) and fine iron powder (10 g, 178 mmol) in acetic acid was stirredat 80° C. until compound 3 completely disappeared monitored by thinlayer chromatography (TLC). The reaction mixture was cooled down to roomtemperature and then precipitated in 5% solution of NaOH. The solid wasfiltered and washed with water several times. Obtained filter cake wasdissolved in hot ethyl acetate (EtOAc) and then filtered to removeunreacted iron, the filtrate was evaporated to remove solvent on arotary evaporator to give4,7-dibromo-5,6-diamine-benzo[1,2,5]thiadiazole 4 as a yellow solid, asconfirmed by the following nuclear magnetic resonance (NMR) dataobtained therefrom: ¹H NMR (500 MHz, DMSO): δ 3.31 (s, 4H) ppm.

Scheme 2 below shows the synthesis of1,2-bis(4-(3-bromopropoxy)-phenyl)ethane-1,2-dione 6 starting from1,2-bis(4-methoxyphenyl)ethane-1,2-dione.

1,2-bis(4-methoxyphenyl)ethane-1,2-dione (5 g, 18.52 mmol) was dissolvedin CH₂Cl₂ and cooled to −78° C. (solid occurred again). BBr₃ (8.3 m,87.82 mmol) was added and mixture was allowed to warm to roomtemperature and stirred for 15 hrs. TLC check showed1,2-bis(4-methoxyphenyl)ethane-1,2-dione completely disappeared. Thereaction mixture was poured into ice, extracted by EtOAc, washed withNaCl solution, dried over MgSO₄. The solvent was removed by vacuum, andthe residue was purified by column chromatography to give compound 5,1,2-bis(4-hydroxyphenyl)ethane-1,2-dione, as confirmed by the followingnuclear magnetic resonance (NMR) data obtained therefrom: ¹H NMR (500MHz, DMSO): δ 10.8 (s, 2H), 7.71 (d, J=8.8 MHz, 4H), 6.90 (d, J=8.8 MHz,4H) ppm.

1,2-bis(4-hydroxyphenyl)ethane-1,2-dione (2.6 g, 10.74 mmol) wasdissolved in DMF and K₂CO₃ (5.9 g, 42.7 mmol) was added, 100 mmol of1,3-dibromopropane and a catalytic amount of KI were then added. Themixture was heated to 80° C. and stirred for 3 days. TLC check showed1,2-bis(4-hydroxyphenyl)ethane-1,2-dione disappeared. Dimethylformamide(DMF) was removed, and water was added, extracted by EtOAc, washed withbrine, dried over MgSO₄. The solvent was removed and the residue waspurified by column chromatography to give1,2-bis(4-(3-bromopropoxy)phenyl)ethane-1,2-dione 6 as a pale yellowsolid, as confirmed by the following nuclear magnetic resonance (NMR)data obtained therefrom: ¹H NMR (500 MHz, CDCl₃): δ 7.94 (d, J=8.8 MHz,4H), 6.99 (d, J=8.8 MHz, 4H), 4.20 (t, J=6.2 MHz, 4H), 3.61 (t, J=6.2MHz, 4H), 2.34 (m, 4H) ppm.

Scheme 3 below shows the synthesis of Monomer 1,4,9-dibromo-6,7-bis(4-(3-bromopropoxy)phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline.

4,7-dibromo-5,6-diamine-benzo[1,2,5]thiadiazole 4 (0.6 g, 1.23 mmol) and1,2-bis(4-(3-bromopropoxy)phenyl)ethane-1,2-dione 6 (0.4 g, 1.23 mmol)were placed in a reaction flask, and AcOH was added. The reactionmixture was heated to 125° C. and stirred for 3.5 hrs. TLC check showedboth compound 4 and 6 disappeared. The mixture was cooled down to roomtemperature and poured into water, and then extracted by EtOAc, washedwith brine, dried over MgSO₄. The residue was purified by columnchromatography to give Monomer 1,4,9-dibromo-6,7-bis(4-(3-bromopropoxy)phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxalineas a orange solid, as confirmed by the following nuclear magneticresonance (NMR) data obtained therefrom: ¹H NMR (500 MHz, CDCl₃): δ 7.77(d, J=8.8 MHz, 4H), 6.95 (d, J=8.8 MHz, 4H), 4.19 (t, J=6.2 MHz, 4H),3.64 (t, J=6.3 MHz, 4H), 2.37 (m, 4H) ppm.

Scheme 4 below shows the co-polymerization of Monomer 1 andthiophene-2,5-diboronic acid to produce Polymer 1.

0.2 mmol of Monomer 1 and 0.2 mmol of 2,5-thiophene-diboronic acid,Pd(PPh₃)₄ (8 mg), K₂CO₃ (0.25 g) were placed in three-neck flask anddegassed, and then refilled with N₂. 20 ml of tetrahydrofuran (THF) and8 ml of water were added, and reaction mixture was heated to 85° C.,stirred for 24 hrs. The reaction was cooled down to room temperature andpoured into CH₃OH. Collected Polymer 1 was washed with CH₃OH severaltimes and dried by vacuum to give a dark solid.

Absorption of Polymer 1 was measured and the spectrum is shown inFIG. 1. Maximum wavelength absorption of energy by the Polymer 1 canreach 1008 nm.

Example 2 Synthesis of Polymer 2 and Water-SolubleGlucose-Functionalized Polymer 2

Scheme 5 shows the synthesis of compound 7,1,2-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)ethane-1,2-dione.

1,2-bis(4-hydroxyphenyl)ethane-1,2-dione (2.6 g, 10.74 mmol) wasdissolved in acetone and K₂CO₃ (5.9 g, 42.7 mmol) was added, then 80mmol of 1-bromo-2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethane was added.The mixture was heated to 80° C. and stirred for 24 hrs. A TLC checkshowed 1,2-bis(4-hydroxyphenyl)ethane-1,2-dione disappeared. Acetone wasremoved, and water was added, extracted by EtOAc, washed with brine,dried over MgSO₄. The solvent was removed and residue was purified bycolumn chromatography to give1,2-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)ethane-1,2-dione7 as a pale yellow oil, as confirmed by the following nuclear magneticresonance (NMR) data obtained therefrom: ¹H NMR (500 MHz, CDCl₃): δ 7.94(d, J=8.8 MHz, 4H), 6.99 (d, J=8.8 MHz, 4H), 4.21 (t, J=4.8 MHz, 4H),3.88 (t, J=4.8 MHz, 4H), 3.80 (t, J=6.3 MHz, 4H), 3.78-3.66 (m, 16H),3.46 (t, J=6.3 MHz, 4H) ppm.

Scheme 6 below shows the synthesis of Monomer 2,4,9-dibromo-6,7-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-[1,2,5]thiadiazolo[3,4-q]quinoxaline.

4,7-dibromo-5,6-diamine-benzo[1,2,5]thiadiazole 4 (0.6 g, 1.23 mmol) and1,2-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)ethane-1,2-dione7 (0.89 g, 1.23 mmol) were placed in a reaction flask, and AcOH wasadded. The reaction mixture was heated to 125° C. and stirred for 3.5hrs. A TLC check showed both compound 4 and 7 disappeared. The mixturewas cooled down to room temperature and poured into water, and thenextracted by EtOAc, washed with brine, dried over MgSO₄. The residue waspurified by column chromatography to give Monomer 2,4,9-dibromo-6,7-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)-phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxalineas an orange sticky oil, as confirmed by the following nuclear magneticresonance (NMR) data obtained therefrom: ¹H NMR (500 MHz, CDCl₃): δ 7.75(d, J=8.8 MHz, 4H), 6.94 (d, J=8.8 MHz, 4H), 4.20 (t, J=4.8 MHz, 4H),3.90 (t, J=4.8 MHz, 4H), 3.82 (t, J=6.3 MHz, 4H), 3.76-3.69 (m, 16H),3.47 (t, J=6.3 MHz, 4H) ppm.

Scheme 7 below shows the co-polymerization of Monomer 2 andthiophene-2,5-diboronic acid to produce Polymer 2.

0.2 mmol of Monomer 2 and 0.2 mmol of 2,5-bis(tributylstannyl)thiophene, Pd(PPh₃)₂Cl₂ (or Pd(PPh₃)₄) (8 mg) wereplaced in a two-neck flask and degassed, and then refilled with N₂. 20ml of THF (or toluene) was added, and reaction mixture was heated to 85°C., stirred for 24 hrs. The reaction mixture was cooled down to roomtemperature and then poured into CH₃OH. Collected precipitate was washedwith CH₃OH several times and recrystallized from CH₂Cl₂/CH₃OH and washedwith CH₃OH again and then dried by vacuum to give Polymer 2 as a blacksolid.

Scheme 8 below shows an example of the conversion of Polymer 2 to abio-molecule derivatized water soluble polymer by attaching glucose toPolymer 2.

0.2 g of Polymer 2 was dissolved in 8 ml of DMF in 25 mL single-neckround bottom flask. 0.2 g of 1-thio-β-D-glucose was added, following by0.5 g of anhydrous K₂CO₃. The reaction mixture was stirred at roomtemperature for 30 hrs, and then transferred into a dialysis tube fordialysis against water for 2 days (8 water changes). The solutionobtained in dialysis tube was then transferred into a single-neck roundbottom flask. After removal of water, Glucose-functionalized Polymer 2was obtained as a black solid.

Glucose-functionalized Polymer 2 has very good water solubility as shownin FIG. 2. Shown on the left is Monomer 2 in CH₂Cl₂ solution. Shown inthe middle is an upper layer of water and a lower layer of Polymer 2 inCH₂Cl₂ solution. Shown on the right is an upper layer ofGlucose-functionalized Polymer 2 in water solution and a lower layer ofCH₂Cl₂.

Example 3 Synthesis of Polymer 3

Scheme 9 below shows the co-polymerization of Monomer 3 andthiophene-2,5-diboronic acid to produce Polymer 3.

0.15 mmol of monomer 3 and 0.15 mmol of 2,5-thiophene-diboronic acid,Pd(PPh₃)₄ (8 mg). K₂CO₃ (0.25 g) were placed in two-neck flask anddegassed, and then refilled with N₂. 10 ml of THF and 5 ml of water wereadded, and reaction mixture was heated to 85° C., stirred for 24 hrs.The reaction mixture was cooled down to room temperature and the waterphase was extracted and transferred into a dialysis tube for dialysisagainst water for 2 days. Then, the water solution in the dialysis tubewas transferred into a single-neck round bottom flask, and the water wasremoved to give Polymer 3 as a dark solid. Polymer 3 has very good watersolubility.

Example 4 Synthesis of Polymer 4

Scheme 10 below illustrates the synthesis of Monomer 4,6,7-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-4,9-bis(5-bromothiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline,starting from Monomer 2.

2.0 g (1.98 mmol) of Monomer 2 and 40 mg ofdichlorobis-(triphenylphosphine) palladium were placed in a 50 mLtwo-neck round bottom flask, degassed and refilled with N₂. AnhydrousTHF was added following by 2-(tribytylstannyl)thiophene (2.3 g, 4.96mmol). The mixture was heated to reflux. After stirring 4 hrs, thereaction mixture was cooled down to room temperature and poured intowater, extracted with EtOAc. Combined EtOAc layer was washed with waterand dried over anhydrous MgSO₄. The solvent was removed and the residuewas purified by chromatography to give Monomer a,6,7-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-4,9-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxalineas a dark blue sticky oil, as confirmed by the following nuclearmagnetic resonance (NMR) data obtained therefrom: ¹H NMR (500 MHz,CDCl₃): δ 9.01 (d, J=4.0 MHz, 2H), 7.81 (d, J=8.8 MHz, 4H), 7.71 (d,J=5.0 MHz, 2H), 7.34 (m, 2H), 6.98 (d, J=8.8 MHz, 4H), 4.23 (t, J=4.8MHz, 4H), 3.94 (t, J=4.8 MHz, 4H), 3.85 (t, J=6.3 MHz, 4H), 3.80-3.72(m, 16H), 3.49 (t, J=6.3 MHz, 4H) ppm.

Monomer a (1.2 g, 1.19 mmol) was dissolved in a 1:1 mixture ofchloroform and acetic acid and N-bromosuccinimide (0.43 g, 2.42 mmol)was added. The reaction mixture was stirred in darkness at roomtemperature for 3 hrs. A TLC check indicated complete reaction, and themixture was poured into water and extracted with EtOAc. The combinedorganic layer was washed with brine solution and dried over anhydrousMgSO₄. After removal of solvent, the residue was purified bychromatography to afford Monomer 4,6,7-bis(4-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethoxy)phenyl)-4,9-bis(5-bromothiophen-2-yl)-[1,2,5]thiadiazolo[3,4]quinoxaline,as a dark sticky oil, as confirmed by the following nuclear magneticresonance (NMR) data obtained therefrom: ¹H NMR (500 MHz, CDCl₃): δ 8.98(d, J=4.0 MHz, 2H), 7.74 (d, J=8.8 MHz, 4H), 7.25 (m, 2H), 6.99 (d,J=8.8 MHz, 4H), 4.24 (t, J=4.8 MHz, 4H), 3.94 (t, J=4.8 MHz, 4H), 3.82(t, J=6.3 MHz, 4H), 3.78-3.71 (m, 16H), 3.47 (t, J=6.3 MHz, 4H) ppm.

Monomer 4 also can be synthesized by other different routes.

Scheme 11 below shows the co-polymerization of Monomer 4 and1,4-phenylenediboronic acid to produce Polymer 4.

0.2 mmol of Monomer 4 and 0.2 mmol of 1,4-phenylenediboronic acid,Pd(PPh₃)₄ (8 mg), KCO₃ (0.25 g) were placed in two-neck flask anddegassed, and then refilled with N₂. 20 ml of THF and 8 ml of water wereadded, and reaction mixture was heated to 85° C., stirred for 24 hrs.The reaction mixture was cooled down to room temperature and then pouredinto CH₃OH. Collected precipitate was washed with CH₃OH several timesand recrystallized from CH₂Cl₂/CH₃OH and washed with CH₃OH again andthen dried by vacuum to give Polymer 4 as a black solid.

Scheme 12 below shows an example of the conversion of Polymer 4 to abio-molecule derivatized water soluble polymer by attaching glucose toPolymer 4.

0.2 g of Polymer 4 was dissolved in 8 ml of DMF in 25 mL single-neckround bottom flask. 0.2 g of 1-thio-β-D-glucose was added, following by0.5 g of anhydrous K₂CO₃. The reaction mixture was stirred at roomtemperature for 30 hrs, and then transferred into a dialysis tube fordialysis against water for 2 days (10 water changes). The solutionobtained in dialysis tube was then transferred into a single-neck roundbottom flask. After removal of water, glucose-functionalized Polymer 4was obtained as a black solid.

Glucose-functionalized Polymer 4 has good water solubility as shown inFIG. 3. On the left is an upper layer of aqueous phase (water) and alower layer of Polymer 4 in CH₂Cl₂ solution. On the right is an upperlayer of glucose-functionalized Polymer 4 in water solution and a lowerlayer of CH₂Cl₂.

Example 5 Synthesis of COOH-Functionalized Polymer 5

Scheme 13 below shows an example of the conversion of Polymer 2 toPolymer 5, with subsequent functionalization of Polymer 5 withcarboxylic acid groups, making COOH-functionalized Polymer 5 watersoluble.

0.3 g of Polymer 2 was dissolved in 8 ml of THF in 25 mL single-neckround bottom flask. 0.4 g of K₂CO₃ was added, following by 0.5 ml ofethyl thioglycolate. After stirring at room temperature for 30 hrs, thewhole mixture was poured into water and then filtered. The obtainedsolid was washed with water 2 times, then washed with CH₃OH severaltimes to yield Polymer 5. The obtained Polymer 5 was directly used to donext step hydrolysis as described below without further purification.

Polymer 5 was dissolved in 10 ml of THF, and a solution of NaOH (2.7 g)in water (1 ml) was added. A few seconds later after adding the NaOHsolution, a large amount of dark precipitates occurred in the reactionmixture. The mixture was stirred for about 5 minutes and thentransferred into a dialysis tube for dialysis against water. The darkprecipitates soon completely dissolved in water in the dialysis tube andthe mixture was dialyzed against water for 2 days (8 water changes). Thesolution in dialysis tube was then transferred into a single-neck roundbottom flask and dried by lyophilization to give COOH-functionalizedPolymer 5 as a dark solid.

COOH-functionalized Polymer 5 has very good water solubility and itsabsorption in water was measured and the spectrum is shown in FIG. 4.Maximum wavelength absorption of energy by the COOH-functionalizedPolymer 5 can reach about 950 nm. The COOH-functionalized Polymer 5shows a broad range of absorption beginning at about 700 nm in thevisible region. The absorption continues past 1100 nm, which is wellinto the NIR region.

Example 6 Immobilization of Biotin to COOH-Functionalized Polymer 5

Scheme 14 below shows an example of the conversion ofCOOH-functionalized Polymer 5 to Biotin-immobilized Polymer 5.

2.0 mg COOH-functionalized Polymer 5 was dissolved in 0.2 ml of 0.1M MESbuffer. 1.0 mg EDC was dissolved in 0.1 mL DI water. 1.0 mg sulf-NHS wasdissolved in 0.1 mL DI water. Then, 27 μl of this EDC solution and 50 μlof this sulf-NHS solution were added to the solution of step 1) and thewhole mixture was incubated for 30 minutes. 1.0 mg biotin was dissolvedin 0.1 ml DMSO. 25 μl of this solution was added to the mixture of step2). The whole mixture was incubated for overnight under gentle stirring

Then, the mixture was transferred into a dialysis tube for dialysisagainst water for 12 hrs (2 water changes). After dialysis, the solutionwas transferred into a vial to dry by lyophilization to giveBiotin-immobilized Polymer 5.

Binding Experiments of Biotin-Immobilized Polymer 5 with StreptavidinCoated Magnetic Beads

The above Biotin-immobilized Polymer 5 was used to incubate withstreptavidin-coated magnetic beads following a reported procedure. Theresults, as observed by the naked eye, are shown in FIG. 5. On the left(FIG. 5A) is shown the binding experimental results for the streptavidincoated magnetic beads plus Biotin-immobilized Polymer 5. In the middle(FIG. 5B) is shown the control experimental results for the streptavidincoated magnetic beads plus COOH-functionalized Polymer 5. On the right(FIG. 5C) is shown only the streptavidin coated magnetic beads.

The binding and control experiments of the streptavidin coated magneticbeads and Biotin-immobilized Polymer 5 described above were carried outunder the same conditions. After incubation, all the beads were washedwith a coupling buffer 4 times. FIG. 5 results are shown for the beadsre-suspended in tris-buffer solution after the 4 washings. A colorchange can be visualized after the binding even without usingfluorescence as signals to see the binding.

For comparative purposes, a commercial available NIR dye labeled biotin,atto 680-biotin, was used to do the same binding experiment. The atto680-biotin used in the binding experiment is the same concentration andvolume as Biotin-immobilized Polymer 5 used in the binding. FIG. 6 showsthe results of beads binding with atto 680-biotin. On the left (FIG. 6A)is shown the atto 680-biotin only. In the middle (FIG. 5B) is shown thebinding of the streptavidin coated magnetic beads and atto 680-biotin.On the right (FIG. 6C) is shown the streptavidin coated magnetic beads.

FIG. 7 shows comparative binding experimental results for magnetic beadsbinding with Biotin-immobilized Polymer 5 and atto 680-biotin. On theleft (FIG. 7A) is shown the binding for the streptavidin coated magneticbeads plus Biotin-immobilized Polymer 5. In the middle (FIG. 7B) isshown the binding for the streptavidin coated magnetic beads plus theatto 680-biotin. On the right (FIG. 7C) is shown the streptavidin coatedmagnetic beads.

Because of the water solubility of the polymers and their opticalproperties in the NIR range, these polymers can be used as fluorescencesignaling reagents in many bio-related applications in the lifesciences, diagnostic testing markets, pharmaceutical market, andenvironmental testing and biological warfare agent detection markets.

The water-soluble polymers above can also be used to form thin films byapplying much lower potential in aqueous solution.

These polymers can often be related to electro-conductive polymers withlow band gaps. With both water soluble and electrically conductiveproperties, the polymers can be used in a biological related system fora number of applications, including as a conductor for electricalsignals of biological origin and otherwise.

Any numbers expressing quantities of ingredients, constituents, reactionconditions, and so forth used in the specification are to be understoodas being modified in all instances by the term “about”. Notwithstandingthat the numeric al ranges and parameters setting forth, the broad scopeof the subject matter presented herein are approximations, the numericalvalues set forth are indicated as precisely as possible. Any numericalvalue, however, may inherently contain certain errors or inaccuracies asevident from the standard deviation found in their respectivemeasurement techniques. None of the features recited herein should beinterpreted as invoking 35 U.S.C. §112, ¶6, unless the term “means” isexplicitly used.

Although the present invention has been described in connection withpreferred embodiments thereof, it will be appreciated by those skilledin the art that additions, deletions, modifications, and substitutionsnot specifically described may be made without departing from the spiritand scope of the invention.

What is claimed is:
 1. A polymeric material comprising: a copolymer of afirst monomer (1), (2) or (3); and a second monomer (4), (5), (6) or(7); wherein,

wherein R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (R₂ can be same ordifferent), SR₂, SR₂COOH, SR₂NH₂, SR₂SO₃H, SR₂SH, SR₂OH, malemide, orNHS ester, X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, orsubstituted heteroaryl, R₂=Alkyl, aryl or heteroaryl, substituted arylor substituted heteroaryl; and n=0, 1, or an integer greater than 1; and

wherein R₃ and R₄=H or


2. The polymeric material of claim 1, further comprising a third monomer(11), (12), (13), (14), (15), (16), (17), (18), or (19); wherein:

wherein R₃ and R₄=H or


3. A polymeric material of claim 1 comprising: a copolymer of a firstmonomer (8), (9) or (10); and the second monomer (4), (5), (6) or (7);wherein,

wherein R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (R₂ can be same ordifferent), SR₂, SR₂COOH, SR₂NH₂, SR₂SOH, SR₂SH, SR₂OH, malemide, or NHSester, X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, or substitutedheteroaryl, and R′=Alkyl, aryl, heteroaryl, substituted aryl orsubstituted heteroaryl.
 4. The polymeric material of claim 3, furthercomprising a third monomer (11), (12), (13), (14), (15), (16), (17),(18), or (19); wherein:

wherein R₃ and R₄=H or


5. The polymeric material of claim 1, further comprising at least onefunctional unit.
 6. The polymeric material of claim 5, wherein the atleast one functional unit comprises one or more of: carbohydrates,proteins, peptides, DNA, RNA, antibodies, antigens, enzymes, bacteria,redox molecules, host molecules, guest molecules, haptens, lipids,microbes, sugars and aptamers.
 7. The polymeric material of claim 5,wherein the polymeric material comprises at least one of the following:

wherein: R₁=OH, Br, I, Cl, SH, COOH, NH₂, N(R₂)₃ (R₂ can be same ordifferent), SR₂, SR₂COOH, SR₂NH₂, SR₂SO₃H, SR₂SH, SR₂OH, malemide, orNHS ester, X=C₀-C₃ alkyl, aryl, substituted aryl, heteroaryl, orsubstituted heteroaryl, R₂=alkyl, aryl or heteroaryl, substituted aryl,substituted heteroaryl, and Y=one or more of carbohydrates, proteins,peptides, DNA, RNA, antibodies, antigens, enzymes, bacteria, redoxmolecules, host molecules, guest molecules, haptens, lipids, microbes,sugars and aptamers.
 8. A polymeric material comprising aself-polymerized product of one of the monomers (1)-(19) as defined byclaim
 4. 9. The polymeric material of claim 7, wherein an absorptionspectrum of the material comprises a maximum wavelength absorption of atleast 600 nm.